Prostaglandin E elevates intraocular pressure and aqueous humor protein in the rabbit and monkey. Cyclic AMP is involved in the actions of prostaglandins. Adenylate cyclase, the enzyme which generates cyclic AMP, and cyclic AMP phosphodiesterase, which inactivates cyclic AMP, exist in the eye. Ciliary process adenylate cyclase is responsive to PGE. Imidazole is a compound which increases the activity of the phosphodiesterase, in vitro. If the PGE ocular effects are related to increased levels of intraocular cyclic AMP, agents which stimulate phosphodiesterase, would antagonize the prostaglandin effect by lowering the cyclic AMP concentration. Preliminary data lend support to this hypothesis. The present proposal is designed to investigate further the above hypothesis in vivo. Intraocular pressure, and aqueous humor protein, cyclic AMP and PGE will be measured in PGE-treated eyes of animals treated or not treated with imidazole and its congeners. Other routes of administration of imidazole will be tested. The effect of imidazole on immunogenic uveitis in the rabbit will be explored. The demonstration of inhibition of an in vivo prostaglandin-induced effect by imidazole would provide evidence of cyclic AMP mediation of these effects and document a new family of potential anti-inflammatory and anti-glaucomatous drugs.